IMAGING SERVICES NORTH Boston Spa, Wetherby West Yorkshire, LS23 7BQ www.bl.uk This PDF was created from the British Library’s microfilm copy of the original thesis. As such the images are greyscale and no colour was captured. Due to the scanning process, an area greater than the page area is recorded and extraneous details can be captured. This is the best available copy D67043ÌB6 \ l ì \ Attention is drawn to ^ the fact that the È copyright o f this thesis rests with its author. This copy o f the thesis has been supplied on condition that anyone who consults it is p- understood to recognise that its copyright rests with its author and that no quotation from the thesis''and no information derived from it may be published without the author’s .pri^^ written consent. - if r>r»FN,..ii Iimm f -pm ' r/. ' Hi. REPRODUCED FROM THE AVAILABLE COPY NEW ASPECTS OF THE MICHAELIS-ARBUZOV AND PERKOW REACTIONS A Thesis SubniittGd. Top the Degpee of* DOCTOR OP PHILOSOPHY of the COUNCIL FOR NATIONAL ACADEMIC AWARDS by Mrs Lubomyra POWROZNYK MSc (Lublin) THE POLYTECHNIC OP NORTH LONDON Holloway Road, London, N? 8 DB October 1985 ACKNOWLEDGEMENTS The authoress owes a great debt and wishes to express her deep gratitude to her supervisor. Dr, H, R. HUDSON, for liis constant guidance, kind patience and helpful discussions during this long investigation. Thanks are also extended to Dr. R. w. Matthews and Mr, J. Crowder for assistance with F and C n.m.r. measurements, and Dr. K. Henrick for X>ray diffraction studies. DECLARATION While registered as a candidate for the degree of Ph.D. for which this subraission is made, I have not been registered as a candidate for any other award. In partial fulfilment of the requirements for the degree, an evening course of MSc lectures on Structural Methods (uv, ir, nmr, mass spectometry and X-ray crystallography) and research colloquia have been attended in the School of Chemistry, Mrs L. Powroznyk ABSTRACT NEW ASPECTS OF THE MICHAELIS-ARBUZOV AND PERKOW REACTIONS Luborayra Powroznyk The work presented in this thesis has involved an inves- gatxonof the thermal decomposition of the Michaelis (o (PhO)5 PMeBr, (PhOjPMel, been shojm to occur by nucleophilic substitution in L e In addition, rnovel^’difpioportionation reactiorgave^tht^™’ 2n r t S quasiphosphonium intermediates and the tetrampfhvi rbrx vx n i ^ salt Which were obtained rrom dispropor by ■>H''"™ p ^ a n d ° §r""® Isolated and identified y n, 1 P, and 1 n.m.r. spectroscopy. In certain C0n t ^ n i n r r p % ® p ‘'?-'‘;i“ ‘*^ proportion of an intermediate -r fu ^ ® linkage was also observed. The mechanisms of these reactions and the spectroscopic features of t h ^ tud T h ^ r S ‘'p n L r ‘^d°"/‘’^ en/produdrhLfbe^e: ^ P-O-P 1 intermediate was isolated in very small amount and was found to be stable in deuterochloroform in a sealed tube, but not as a solid. «^^erocnioroform in hindered phosphorus (III) esters viy (R0 )3 P, (R0 )2 PPh, and R0PPh2 (R = Me3 CCHo), th^f^rst examples of identifiable intermediates ?ROU p+ph p h L r Ph2 Pi(0R)CH2 cSphB;-, ani "^COPhBr-, Ph2 PMORloct:CH2 )PhCl- L v e been^obtained ?n the reactions bv intermediates have been investig^Ud ^ H n.m.r. spectroscopy and the mechanisms^nC their decomposition to Arbuzov and Perkow uroducts hot/o been elucidated. The intermediates PhP+(OR)oGHorr>Pv r - rnriCDir^°L^'^? 2CpPhBr: were suaoiestable ata? roomr o o m temp ' S e r ^ t u r " f L CDCICDOI5.. heating in sealed tubes (O-R(0.5 h)i atq ^-^i o O ^ c ) 3 the dilute solutions decomposed completely to sive nnn^ products of PhP(0)(0R)CH2 C0Ph and of PhoPf0 )cLrnPh respectively. Neopentyl gromide was f S i ^ L c h case. studies on the réaction*^ nc \ 1- have also revealed a competing process of P-N cleavaee o?\hfh"îid: p“î:::^nt!" the'=^:?d^nf:s 1.1 MICHAELIS-ARBUZOV REACTION Tlie interaction of trialkyl phosphites and alkyl hali- des, referred to as the Michaelis-Arbuzov reaction, was first reported by Michaelis^ and later exploited extensi- vely by Arbuzov'^ and many other workers. (RO)^P + R'X (R0)2P(0)R' + RX A stable 1:1 intermediate was obtainable in certain instances from triaryl phosphites^-® and in other special cases involving trialkyl phosphites and a,p-dihaloalkyl ethers, ^ ^ The first step in this type of reaction was made by Michaelis and Kahne, who reported in 1898 that the reac­ tion of triphenyl phosphite with iodomethane at 100 °C for 48 h yielded 1 :1 adduct as crystalline needles, m.p. 70- 75 (C^H^O)^P + CH^I (CgH^O)^PCH^I Adducts of this type are generally known as quasiphos- phonium intermediates * ^ and are readily hydrolysed to give the phosphonate, phenol, and hydrogen iodide. (C6H^0)^PCH^I + H*0H — ^ HI + C^H^OH + CH^P0(0C^H^ Michaelis and Kahne prepared a number of other interme­ diates e.g. from tri-m-tolyl or tri-p-tolyl phosphite and iodomethane by heating the reactants together on a water bath, Tri-ni-tolyl phoaphite waü thus heated for 5 h to give a dark brown oily liquid, which became crystalline after cooling, and after washing with dry ether it gave a hygroscopic crystalline product.^ The product from tri-p-tolyl phosphite, obtained after 12 h, remained however as a viscous liquid.^* Triphenyl phosphite and benzyl chloride gave a syrupy liquid on heating at 150-175 °C, instead of the expected crystalline phosphonium compound, A number of aromatic intermediates were also produced by Arbuzov in 1906, but both Michaelis and Arbuzov failed to obtain intermediates from trialkyl phosphites and alkyl halides. They showed that the final products in these reactions were usually phosphonates and alkyl halides, although Michaelis and Kahne obtained methylphosphonic acid, ethyl iodide and ethene by heating triethyl phosphi­ te with methyl iodide at 110-220 °C for 12 h. (G2H^0 )^PCH^I > J CH^POiOH)^ + C^H^I + They assumed from the beginning that a phosphoniuia intermediate was involved: (RO)^P + R»X -* 1(r o ),p r ':^ The thermal decomposition of triphenyl phosphite-alkyl halide adducts was investigated by Arbuzov^^ in 1905, by heating the compounds in sealed tubes at 210-220 °C. Some tar formation occurred, especially with the higher mem­ bers, along with free iodine, and the following decomposi- tion products were isolated. Temp. Time Yield (%) Adduct n (h) Phi RP(0)(0Ph)2 (PhO)^PMel 220 20 74 56 ^ (PhO)^PEtl 220 20 71 60 - (PhO)-PCH. ,PhI 208 20 J 2 15 a 196-9 °C, 1.5520 b b ^2 200-4 °C, 1.5454 The isobutyl iodide adduct, however, gave only iodine as the isolated product after 15 h at 210 °G. The Michaelis-Arbuzov reaction^^ takes place with any derivative of trivalent phosphorus that carries an ester group (OR): > - 0 R + R»X — > 1P(0R)R» X — ► P(0)R' + RX and most varied selection of organic halides R ’X are able to participate in the reaction. The chief requirement of the structure of the organic halide is that the halogen atom must be capable of nucleophilic displacement, this occurring most easily if it is attached to the terminal carbon atom of an aliphatic chain. It must not be directly connected to an aromatic ring. The above reaction is merely one instance of the more general Michaelis-Arbuzov rearrangement, ^ or isomerisa­ tion. If the radical R» of the alkyl halide is identical with the radical R of the ester group the reaction takes on the aspect of a true isomerisation,^^ which can be performed with minute amounts of the halide R'X. Landauer and Rydon thus shoived that isomerisation^ of trimethyl phosphite occurred with methyl iodide (0.1 mol) by heating the reactants under reflux at 100 °C. After a brief induction period, a vigorous reaction set in and was complete within 5 min. Distillation then gave methyl iodide and dimethyl methylphosphonate: (MeO)^P + Mel (Me0)2P(0)Me + Mel Although customarily used with tertiary phosphites, (RO)^P, from which the reaction product is an ester of a primary phosphonic acid R»P(0)(0R )2 i.e. a PHOSPHONATE,^^ the reaction may also be carried out with esters of phos- phonous acids, RP(0R)2, in which case esters of secon- ^ r y phosphonic acids R»RP(0)0R, i.e. PHOSPHINATES are formed. RP(0R)2 + R»X — ^ R'RP(0)0R + RX Esters of phosphinous acids, R^POR, form tertiary phosphine oxides R^P=0 as follows: R^POR + R»X R2R’P=0 + RX The reactivity of phosphorus (III) esters increases from phosphites to phosphonites and again to phosphinites, in accord with a general increase in reactivity upon approach to the tertiary phosphine structure.^ Although the reaction is frequently conducted by mixing the reactants and warming the mixture to the required tem­ perature,'*^ most often IOO-I5O °C, the most reactive combi­ nations enter the reaction at room temperature, this being especially true of reactions with acyl halides. Crystalline quasipliosphonium salts^^ have in some cases been prepared by the addition of methyl iodide to unsaturated phosphonous diesters containing branched ester radicals, such as GH2=CH-CH2 P(OBu^)^, although the adducts decompose to secondary phosphoric esters on mild heating; 0 CH2=CH-CH2P'"(0Bu ^)^RX~ — » CHp= CH-OBu^ + Bu^X The phosphonous diesters are also more susceptible to self-isomerisation than the trialkyl phosphites, but in a truly pure state they isomerize with difficulty.